1. Field of the Invention
The present invention relates generally to a sensor system, and more specifically to a sensor for detecting biological and chemical agents in the environment.
2. Description of the Related Art
Antibody-based detection systems are the most mature and advanced technology for biological agent detection and identification. Antibodies are defined as any of the body immunoglobulins that are produced in response to specific antigens and that counteract their effects by neutralizing toxins, agglutinating bacteria or cells, and precipitating soluble antigens. Antigens are defined as protein or carbohydrate substances capable of stimulating an immune response. Antibodies are very specific and bind only to their target, even in the presence of other material. In a detector, antibodies are normally immobilized on a substrate, e.g., a polymer, such as polyvinylethylene, polyethylene, or polystyrene, for subsequent incubation with the target organism or molecule. Typically, the antibodies are not chemically bound to the substrate, but merely attached by hydrogen bonding or electrostatic charge. The antibody and antigen bind upon contact, thereby immobilizing the antigen. Classically, a second antibody to the target agent incubates, as well as binds to the antigen. This second antibody is generally linked to some type of reporter system, usually an enzyme. The varying forms of these reporter systems include, e.g., fluorescent, magnetic, enzymatic, colorimetric, etc. This transducer provides the means of detecting the presence of the antigen of interest. Enzyme linked immunosorbent assay (ELISA) is based on this process.
An analyte in the antibody-antigen detection system is typically in an aqueous solution or other liquid solution. The aqueous solution must make frequent and intimate contact with the immobilized antibody on the substrate material. A large surface area on the substrate allows a higher density of antibodies and hence a higher sensitivity. However, the antibodies must be tightly bound to the substrate to survive repeated motion of the analyte over the substrate without becoming detached and flushed away with the solution. Therefore, covalent bonding, rather than hydrogen bonding or electrostatic bonding, of the antibodies to the substrate is preferential. Many biological compounds of interest in the system are proteins, e.g., enzymes, hormones, toxins, antibodies, and antigens. Proteins are composed of amino acids, having both an amino group (NH2) and a carboxylic acid group (COOH). A substrate functionalized with one or both of these groups can be activated to chemically bind antibodies.
The introduction of a second antibody in the ELISA process complicates and slows down the detection/identification process. A physical property change produced by the antibody-antigen chemical reaction provides the basis for a more direct transduction mechanism. The transduction mechanism in an optics-based detection system is based on a change in absorption or index of refraction, which is monitored by the optical system.
Several detectors are based on a change of index of refraction. One such sensor is based on surface plasmon resonance. Surface plasmon techniques are difficult to integrate for multiplexed operation where multiple target agents can be monitored simultaneously. Also, their sensitivity cannot be engineered by sharpening the spectral or angular response to light.
Other known sensors include a chemical sensor based on porous silicon and a porous-semiconductor-based, e.g., porous Si, optical interferometric sensor. Interference filters can be made with porous silicon. However, porous silicon interference filters are incompatible with polymer waveguide technology and hence cannot be readily integrated onto a polymer waveguide chip. Also, porous polymers are easier to apodize, i.e., sharpen, their spectral response using holographic techniques. Moreover, polymer chemistry is more adaptable to functionalization with chemical groups for binding antibodies and antigens. Most immunosorbent assays are conducted on polymer substrates. Porous silicon has not been widely used for this application. No conventional methods propose the simultaneous use of porous semiconductors as both chemical and optical filters.
Another known sensor is a doubly-differential interferometer-based sensor with evanescent wave surface detection. This sensor is a surface detector only and cannot take advantage of the extended surface area of a porous polymer. Furthermore, the sensor also requires polarized light and a modulator. Additionally, this sensor is a part of a system that does not provide for continuously monitoring the environment. The interferometer is also not flexible for sharpening the optical response for higher sensitivity.
Another sensor, in the form of polymerized crystalline colloidal arrays, achieves detection of chemical and biological agents by a change in diffraction accompanying the swelling or shrinkage of a hydrogel containing the crystalline colloidal array in response to a chemical reaction with target agent(s). Similarly, a conventional hologram-containing sensor consists of a holographic grating recorded preferably in a gelatin, where reaction of chemical agents with the gelatin produces some change in the physical properties of the hologram matrix, thereby changing the diffraction properties of the hologram. In both the polymerized crystalline arrays and the hologram-containing sensor, a matrix containing a grating serves to uptake an analyte, but does not allow for the analyte to flow through the system. Once the system is swollen, the only mechanism for replacing it with new samples is to remove the grating from the system and dry it out. Since the materials used are not porous, the system cannot take advantage of increased surface area to volume ratio and does not provide a convenient method for chemically filtering the analyte. These methods are also not compatible with waveguides for integration onto a chip.
Another chemical and biochemical sensor includes a planar waveguide with a grating coupler. A recognition layer containing specific chemical or biochemical binding partners, e.g., antibodies or antigens, is located on the waveguide. A chemical reaction on the recognition layer changes the effective refractive index of the guiding layer, thereby changing the coupling efficiency of the grating, i.e., the angle of incidence for maximum input coupling to the waveguide. Using this sensor, a method for optical determination of an analyte records the position of light points with a position sensitive detection method. The grating is a surface grating formed by standard methods, i.e., photolithographic patterning followed by etching. A surface grating sensor cannot take advantage of the extended surface area of a porous polymer, since the grating cannot be extended throughout the volume of the porous polymer and chemical detector or recognition molecules cannot be dispersed throughout the volume to increase its chemical sensitivity. This system does not provide a mechanism for continuously monitoring the environment by flowing the analyte through the grating, since it is only a surface grating. Nor does the system use the grating as an optical filter to take advantage of the sharp spectral properties of a Bragg grating for detecting large changes in transmission of such a filter with relatively small changes in refractive index.